Results of the largest retrospective study comparing the clinicopathologic characteristics of patients with acute undifferentiated leukemia with those with acute myeloid leukemia with minimal differentiation were published in Modern Pathology.
Most cases of acute leukemia can be classified as having either a myeloid or lymphoid lineage. In order to classify acute leukemia with a mixed-phenotype, the World Health Organization (WHO) proposed in 2008 that leukemia characterized by the presence of myeloperoxidase or evidence of monocytic differentiation as identified by 2 or more markers, including nonspecific esterase cytochemistry, CD11c, CD14, or CD64, be classified as acute myeloid leukemia.
A subset of acute myeloid leukemia not associated with the presence of peroxidase but showing expression of at least 2 of myeloid markers is included as the subtype under acute myeloid leukemia of “not otherwise specified” according to the WHO classification system, and is referred to as “acute myeloid leukemia with minimal differentiation.”
Regarding acute lymphoblastic leukemia, T-lineage was defined in the WHO system by cytoplasmic or surface CD3, and staining intensity comparable to that of background T cells in a subset of blasts. Finally, B-lineage was defined being characterized by multiple antigens, including CD10 in combination with CD79a, cytoplasmic CD22 and/or CD10.
However, a small number of acute leukemia cases do not meet the criteria for either acute myeloid or acute lymphoblastic leukemia. In rare cases where no lineage-specific markers are present, the classification of “acute undifferentiated leukemia” is made.
In 2016, the WHO revised its classification system for “acute myeloid leukemia with myelodysplastic changes,” which corresponds to acute myeloid leukemia occurring following a history of myelodysplastic-associated abnormalities. Hence, acute undifferentiated leukemia is now classified as acute myeloid leukemia with myelodysplastic changes if a history of myelodysplastic-associated changes is present and certain recurrent genetic abnormalities (eg, characterized by a NPM1 or CEBPA mutation) are absent.
The main purpose of the current study was to compare cytogenetic and molecular features of leukemia classified as acute myeloid leukemia with minimal differentiation with those classified as acute undifferentiated leukemia.
Databases from Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Cleveland Clinic, Massachusetts General Hospital, MD Anderson Cancer Center, Stanford Health Care, University of Chicago, University of Pennsylvania, and Weill Cornell Medical Center were mined for clinical and pathologic data on patients with diagnoses of acute undifferentiated leukemia or acute myeloid leukemia with minimal differentiation (based on WHO classifications from 2008 and 2016).
Of the 54 patients included in the main study, 24 and 30 were assigned the acute undifferentiated leukemia and acute myeloid leukemia with minimal differentiation groups, respectively. In addition, 32 patients with disease characterized as acute myeloid leukemia with myelodysplastic changes based on the 2016 WHO criteria were also identified.
Although patients diagnosed with acute undifferentiated leukemia had disease that was more likely to be characterized by a higher PHF6 mutation frequency (P =.016), more frequent blast expression of TdT (P =.003), and a lower likelihood of CD123 expression (P =.042) compared with patients with a diagnosis of acute myeloid leukemia with minimal differentiation, no significant differences in clinical outcomes were observed between the 2 groups.
Interestingly, after censoring for bone marrow transplant, patients with disease classified as acute myeloid leukemia with myelodysplastic changes based on patient history had significantly worse survival compared with patients with acute undifferentiated leukemia (P =.03) and patients with acute myeloid leukemia with minimal differentiation (P =.002).
In their concluding remarks, the study authors noted that “the outcome of patients with acute myeloid leukemia with myelodysplasia-related changes was significantly worse than de novo acute undifferentiated leukemia, which supports the WHO classification of cases with history of prior myelodysplastic syndrome and/or myelodysplastic syndrome-type karyotype findings as acute myeloid leukemia with myelodysplasia-related changes.”
Weinberg OK, Hasserjian R, Baraban E, et al. Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group . Mod Pathol. doi: 10.1038/s41379-019-0263-3